Elsevier

Cancer Epidemiology

Volume 36, Issue 6, December 2012, Pages 533-536
Cancer Epidemiology

Expression of 14-3-3γ in patients with breast cancer: Correlation with clinicopathological features and prognosis

https://doi.org/10.1016/j.canep.2012.05.003Get rights and content

Abstract

Aim

Protein 14-3-3γ is an important member of the 14-3-3 family that play important roles in the regulation of various cellular processes. The aim of the study is to investigate the association between 14-3-3γ expression and the clinicopathological features of patients with breast cancer.

Methods

The expression of 14-3-3γ was detected by Western blot in both foci of breast cancer and adjacent non-cancerous tissues. In addition, 14-3-3γ expression was analyzed by immunohistochemistry in 60 clinicopathologically characterized breast cancer cases. The association of 14-3-3γ expression with survival of the patients were analyzed.

Results

The expression level of 14-3-3γ protein in breast cancer were significantly higher than that in non-cancerous mammary gland tissues. Moreover, high expression of 14-3-3γ correlated with tumor size and tumor grade (all P < 0.05). Patients with high 14-3-3γ expression had worse overall survival rate than that with low expression (P < 0.05). Furthermore, multivariate analysis showed that 14-3-3γ expression was an independent predictor of overall survival (HR, 0.196; 95%CI, 0.043–0.892; P = 0.035).

Conclusions

Our data suggest for the first time that the increased expression of 14-3-3γ in breast cancer is associated significantly with tumor progression and poor prognosis. 14-3-3γ may be a novel and potential prognostic marker for breast cancer.

Introduction

Breast cancer is one of the most common malignancy in women, and its incidence has recently increased [1]. The diagnosis and treatment of breast cancer usually depended on a subset of clinical markers that predict clinical outcomes and therapeutic effects. Overexpression of Her-2 is a well-characterized prognostic biomarker for adverse clinical outcome in breast cancer patients [2]. Identification of more effective markers would facilitate better understanding of the molecular mechanism of breast cancer. More importantly, these markers may lead to the development of new therapies to provide more effective therapies for cancer patients.

The 14-3-3 family have been found to play important roles in the regulation of various cellular processes, such as cell cycle progression, cell growth, apoptosis, signal transduction and malignant transformation [3], [4], [5]. 14-3-3γ belongs to a family of abundant, widely expressed 28–33 kDa acidic polypeptides. In humans, there are seven closely related genes encoding β, ɛ, γ, ζ, σ, η, and τ isoforms [6]. 14-3-3ζ overexpression occurs in early staged breast diseases and contributes to transformation of human mammary epithelial cells [7]. However, 14-3-3σ protein levels are significantly reduced or negligible in various primary tumors of epithelial origin, including breast cancer and hepatocellular carcinoma [8], [9]. Therefore, 14-3-3 proteins have complex functions in tumorigenesis.

In hepatocellular cancer, Lee et al. [10] detected the presence of 14-3-3γ overexpression by two-dimensional difference gel electrophoresis. In addition, Qi et al. [11] demonstrated that overexpression of 14-3-3γ protein in human lung cancer cell line H322 results in abnormal DNA replication and polyploidization. However, the status of 14-3-3γ protein and its possible roles have never been examined in breast cancer. To date, no report has been found on the relationship between 14-3-3γ expression and clinicopathological factors in breast cancer. In order to explore the clinical significance of 14-3-3γ in the development of breast cancer, we investigated 14-3-3γ protein expression in 60 cases of breast cancer and correlated the findings with clinical outcomes of the patients.

Section snippets

Tumor specimens

A total of 60 unselected breast cancer samples were collected between January 1994 and January 1995 from the first affiliated hospital of Guangdong Pharmaceutical University. All patients had had no previous surgery to the breast and did not receive preoperative treatment. For immunohistochemistry analysis, these breast cancer cases included 60 patients, with mean age of 52 years (range, 33–71 years). Clinicopathologic characteristics for these patients including age, tumor size, tumor grade,

Expression of 14-3-3γ in breast cancer tissues

The expression of 14-3-3γ protein in breast carcinoma samples and normal mammary glands adjacent to tumor were analyzed by immunohistochemistry. 14-3-3γ was predominantly expressed in the cytoplasm of tumor cells, and 63% (38/60) of breast cancer specimens showed high expression of 14-3-3γ, in contrast to weak or no expression in normal mammary gland tissues. Typical 14-3-3γ immunostaining in normal and cancer were shown in Fig. 1.

To confirm the results observed from immunohistochemistry, we

Discussion

This study examined the expression of 14-3-3γ protein and its correlation with clinicopathologic parameters in breast cancer for the first time. In the present study, overexpression of 14-3-3γ protein was confirmed by western blot and immunohistochemistry analysis respectively. Overexpression of 14-3-3γ was correlated with larger tumor size. Moreover, 14-3-3γ expression was significantly higher in tumor grade III than in those in grade I and II. These results suggest that 14-3-3γ expression may

Conflict of interest statement

There are no conflicts of interest to declare.

Acknowledgment

This work was supported by Initial Doctoral Funding of Guang Dong Medical College.

References (22)

  • A. Aitken et al.

    14-3-3 proteins: a highly conserved, widespread family of eukaryotic proteins

    Trends Biochem Sci

    (1992)
  • A. Aitken

    14-3-3 proteins a historic overview

    Semin Cancer Biol

    (2006)
  • Y.H. Jin et al.

    Sirt2 interacts with 14-3-3beta/gamma and down-regulates the activity of p53

    Biochem Biophys Res Commun

    (2008)
  • A. Jemal et al.

    Cancer statistics

    CA Cancer J Clin

    (2007)
  • M.F. Press et al.

    Her-2/neu expression in node-negative breast cancer: direct tissue quantitation by computerized image analysis and association of overexpression within creased risk of recurrent disease

    Cancer Res

    (1993)
  • M.K. Dougherty et al.

    Unlocking the code of 14-3-3

    J Cell Sci

    (2004)
  • C. Mackintosh

    Dynamic interactions between 14-3-3 proteins and phosphoproteins regulated inverse cellular processes

    Biochem J

    (2004)
  • C.L. Neal et al.

    14-3-3ζ overexpression defines high risk for breast cancer recurrence and promotes cancer cell survival

    Cancer Res

    (2009)
  • N. Iwata et al.

    Frequent hypermethylation of CpG islands and loss of expression of the 14-3-3 sigma gene in human hepatocellular carcinoma

    Oncogene

    (2000)
  • M. Nacht et al.

    Combining serial analysis of gene expression and array technologies to identify genes differentially expressed in breast cancer

    Cancer Res

    (1999)
  • I.N. Lee et al.

    Identification of human hepatoceullular carcinoma-related biomarkers by two-dimensional difference gel electrophoresis and mass spectrometry

    J Proteome Res

    (2005)
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